MedCheck: Brexpiprazole and PTSD, Lumateperone for MDD, Subcutaneous Buprenorphine, and more

In June Otsuka Pharmaceutical, Co. Ltd. and H. Lundbeck A/S announced that the Food and Drug Administration (FDA) has accepted for review a supplemental New Drug Application (sNDA) for Rexulti (brexpiprazole) in combination with sertraline for the treatment of adults with posttraumatic stress disorder (PTSD). The sNDA submission is based on data from three randomized clinical trials that evaluated the safety and efficacy of brexpiprazole in combination with sertraline in adults with PTSD.

The primary endpoint for all three trials was the change from randomization to week 10 on the Clinician-Administered PTSD Scale (CAPS-5) total score for brexpiprazole and sertraline combination therapy compared with sertraline plus placebo. In both Trial 061 (a phase 2 flexible-dose trial) and Trial 071 (a flexible-dose phase 3 trial), patients who took brexpiprazole plus sertraline had a statistically significant greater reduction in CAPS-5 score (between 16-19 points), compared with patients who took sertraline plus placebo. Although the fixed-dose phase 3 Trial 072 did not meet its primary endpoint, patients who took brexpiprazole in combination with sertraline had similar reductions in PTSD symptoms as patients who took this combination in the other trials.

Across all three trials, 55.5% of patients who took brexpiprazole plus sertraline and 56.2% of those who took sertraline plus placebo reported treatment-emergent adverse events.

In a phase 3 trial, patients with major depressive disorder (MDD) who took Caplyta (lumateperone) daily along with their antidepressants experienced a greater reduction in symptoms than patients who took only antidepressants, Intra-Cellular Therapies announced in June.

In Study 502, 480 adults whose major depressive disorder was not adequately treated with antidepressants alone were randomized to add either 42 mg lumateperone or placebo for 6 weeks. The baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores were 30.8 for the lumateperone group and 31.5 for the placebo group. At the end of six weeks, the lumateperone group’s mean MADRS dropped 14.7 points compared with 10.2 points in the placebo group. Those in the lumateperone group also had a statistically greater reduction on the Clinical Global Impression Scale for Severity of Illness compared with those taking placebo.

This is the second phase 3 study to show improvement in MADRS scores for patients who take lumateperone with their antidepressants. In Study 501, 485 patients with major depressive disorder were randomized to receive 42 mg of lumateperone or placebo once per day along with their usual antidepressants. At week 6, patients in the lumateperone group experienced a mean reduction in MADRS score of 14.7 points, compared with 9.8 points in the placebo group.

Subcutaneous buprenorphine may be more effective than sublingual buprenorphine-naloxone for treating opioid use disorder (OUD) in people who use fentanyl, a study published in JAMA Open Network in June has found. The findings are from a post hoc analysis of a phase 3 randomized 24-week clinical trial in 428 adults with OUD.

In that trial, participants were randomized to receive either daily sublingual buprenorphine-naloxone tablets (up to 24 mg/d) and weekly subcutaneous placebo injections or daily sublingual placebo tablets and weekly subcutaneous buprenorphine injections (≤32 mg/week) for 12 weeks. Afterwards, the subcutaneous injections transitioned from weekly to monthly administration (subcutaneous buprenorphine ≤160 mg/mo or matching placebo) for 12 more weeks.

Overall, 123 participants had evidence of fentanyl use at baseline and 305 did not. At study’s end, the percentages of urine samples negative for opioids in the fentanyl group were 28.5% for subcutaneous buprenorphine and 18.8% for buprenorphine-naloxone. In addition, the percentages of urine samples negative for fentanyl in this group were 74.6% for subcutaneous buprenorphine and 61.9% for buprenorphine-naloxone.

The percentages of urine samples negative for opioids in the non-fentanyl group were 36.7% for subcutaneous buprenorphine and 30.6% for buprenorphine-naloxone. Opioid withdrawal and craving diminished rapidly across both groups.

In a phase 3 clinical trial, patients with MDD and insomnia who took seltorexant, an investigational selective orexin-2 receptor antagonist, reported greater improvements in both depressive symptoms and sleep disturbances than those who took placebo, Johnson & Johnson announced in May. The trial’s results were presented at the American Society of Clinical Psychopharmacology Annual Meeting.

The trial included 588 patients whose depressive and insomnia symptoms were not adequately treated on an SSRI or an SNRI alone. Participants were randomly assigned to receive seltorexant 20 mg or placebo once daily along with their antidepressant for 6 weeks.

At week six, MADRS total scores decreased a mean of 2.6 points more in participants who took seltorexant compared with those who took placebo. Compared with those taking placebo, participants in the seltorexant group also experienced a mean greater decrease of 2 points on the MADRS excluding sleep questions and 3.7 points on the Patient Reported Outcome Measurement Information System-Sleep Disturbance T-score. ■